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    Elucidating the Role of Lasp-2 in Cell Adhesion and Migration

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    Author
    Bliss, Katherine Theresa
    Issue Date
    2012
    Keywords
    Cytoskeleton
    Migration
    Nebulin
    Cell Biology & Anatomy
    Actin
    Adhesion
    Advisor
    Gregorio, Carol C.
    
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    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Embargo
    Release after 20-May-2013
    Abstract
    In order for cells to migrate, communicate, and facilitate attachment to the surrounding extraceullar matrix, they must form intricate protein complexes called focal adhesions. The number of identified focal adhesion components continues to grow and the field is an area of active study.Lasp-2 is a member of the nebulin family of actin-binding proteins that has been identified as a member of focal adhesion complexes. To gain further insights into the functional role of lasp-2, we identified two additional binding partners of lasp-2, the integral focal adhesion proteins, vinculin and paxillin. Interestingly, the interaction of lasp-2 with its binding partners vinculin and paxillin was significantly reduced in presence of lasp-1, another nebulin family member. The presence of lasp-2 appears to enhance the interaction of vinculin and paxillin with each other, however, as with the interaction of lasp-2 with vinculin or paxillin, this effect is greatly diminished in the presence of excess lasp-1 suggesting the interplay between lasp-2 and lasp-2 could be an adhesion regulatory mechanism. Lasp-2's potential role in metastasis was revealed as overexpression of lasp-2 in SW620 cells, a highly metastatic cancer cell line, increased cell migration, but impeded cell invasion.Lasp-2 transcript and protein is readily detected in neural tissues. Preliminary experiments involving the knockdown of lasp-2- in frog embryos revealed gross morphological abnormalities in the head region as well as the inability to move normally. Neural crest derived melanocytes also failed to migrate normally.Taken together, these data suggest that lasp-2 has an important role in coordinating and regulating the composition and dynamics of focal adhesions.
    Type
    text
    Electronic Dissertation
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Cell Biology & Anatomy
    Degree Grantor
    University of Arizona
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